Gut Microbiota and the Neuroendocrine System

Neurotherapeutics. 2018 Jan;15(1):5-22. doi: 10.1007/s13311-017-0600-5.


The microbial ecosystem that inhabits the gastrointestinal tract of all mammals-the gut microbiota-has been in a symbiotic relationship with its hosts over many millennia. Thanks to modern technology, the myriad of functions that are controlled or modulated by the gut microbiota are beginning to unfold. One of the systems that is emerging to closely interact with the gut microbiota is the body's major neuroendocrine system that controls various body processes in response to stress, the hypothalamic-pituitary-adrenal (HPA) axis. This interaction is of pivotal importance; as various disorders of the microbiota-gut-brain axis are associated with dysregulation of the HPA axis. The present contribution describes the bidirectional communication between the gut microbiota and the HPA axis and delineates the potential underlying mechanisms. In this regard, it is important to note that the communication between the gut microbiota and the HPA axis is closely interrelated with other systems, such as the immune system, the intestinal barrier and blood-brain barrier, microbial metabolites, and gut hormones, as well as the sensory and autonomic nervous systems. These communication pathways will be exemplified through preclinical models of early life stress, beneficial roles of probiotics and prebiotics, evidence from germ-free mice, and antibiotic-induced modulation of the gut microbiota.

Keywords: Antibiotics; Corticosterone; Germ-free mice; HPA axis; Probiotics; Stress.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / adverse effects
  • Dysbiosis / chemically induced
  • Dysbiosis / microbiology
  • Gastrointestinal Hormones / metabolism
  • Gastrointestinal Microbiome*
  • Humans
  • Hypothalamo-Hypophyseal System / microbiology*
  • Mice
  • Pituitary-Adrenal System / microbiology*
  • Stress, Psychological / microbiology


  • Anti-Bacterial Agents
  • Gastrointestinal Hormones